Our laboratory has been interested in the role of absorbed bacterial endotoxins in the initiation and perpetuation of injury in structurally or metabolically altered livers. We have previously shown that reticuloendothelial function necessary for endotoxin detoxification is impaired by alcohol administration and choline deficiency, and that rats with nutritional fatty livers are extremely sensitive to the hepatoxic effects of endotoxin. The present project proposes to further study hepatic effects of endotoxin by: 1) attempting to detect endotoxin in sera, ascites and liver biopsy specimens of patients with alcoholic hepatitis and other forms of liver disease, 2) studying tissue distribution of labeled endotoxin in states of experimental liver injury, and half-time endotoxin clearance in intact animals and in the isolated perfused choline-deficient fatty liver, 3) studying endotoxin absorption through everted gut sacs from animals given alcohol, starved, or with liver injury, 4) studying the possible role of endotoxin in the experimental hepato-renal syndrome, 5) extending our observations on the protective effect of non-specific endotoxin tolerance on liver injury to the effect of more specific immunization, and 6) extending the studies on the ability of cholestyramine resin to bind endotoxin and reduce its toxicity and absorption.